Our understanding of the physiologic control of digestive systems is increasing. Many observations suggest a sympathetic nervous system influence directly on the exocrine pancreas. Concomitantly, observations of cholinergic and adrenergic imbalance in patients with cystic fibrosis are known, suggesting that dysfunction of the autonomic nervous system may contribute to the pathogenesis of cystic fibrosis. To define alpha and beta adrenergic receptor mediated influences on exocrine pancreatic enzyme secretion is the objective of this proposal. Acute and chronic surgical preparations have been used to describe pancreatic exocrine response to physiologic stimuli. Other in vivo animal studies including our own, have examined the effects of adrenergic agents on pancreatic secretion. Interpretation of these results is difficult because of dramatic cardiovascular effects of adrenergic agents. Whether an observed response is caused by changes in blood flow or is due to direct effects on exocrine glands frequently cannot be determined. This proposal describes an in vitro system, dispersed pancreatic acini from guinea pig or rat pancreas, to study pancreatic enzyme secretion. This experimental preparation, dispersed pancreatic acini, will permit the study of direct effects of adrenergic agents (norepinephrine, epinephrine, isoproterenol, terbutaline, and phenylephrine) on basal and hormone stimulated amylase release and calcium efflux from these isolated cells. This in vitro preparation will also be applied to an animal model for cystic fibrosis, the chronically reserpinized rat. We will determine the cholinergic, hormonal, and adrenergic responses from dispersed pancreatic acini prepared from reserpine treated rats. These observations will help determine whether a role exists for the sympathetic nervous system in the physiologic modulation of pancreatic enzyme secretion and may be helpful in understanding the pathophysiology of cystic fibrosis. Ultimately, this new information may suggest specific medical or surgical treatment for children afflicted with this common inherited disease.